Previously, poly (N-isopropylacrylamide) [p(NIPAAm)] homopolymer chains, copolymer chains, crosslinked hydrogels and p(NIPAAm)-based sIPNs (and also IPNs, which consist of two cross-linked networks that are physically entangled within each other but are not chemically connected in any way) have been studied for use in a number of diverse applications including solute recovery, (Freitas et al., Chemical Engineering Science, 42:97-103 (1987)) solute delivery, (Hoffman et al., Journal of Controlled Release, 4:213-222 (1986); Vakkalanka et al., Journal of Biomaterials Science, Polymer Edition, 8:119-129 (1996)) cell adhesion and manipulation, (Okano et al., Journal of Biomedical Materials Research, 27:1243-1251 (1993)) bioseparations, (Monji et al., Applications in Biochemistry and Biotechnology, 14:107-120 (1987)) catalytic reaction control, (Park et al., Biotechnology Progress, 7:383-390 (1991)) microencapsulation of cells, (Shimizu et al., Artificial Organs, 20:1232-1237 (1996)) chromatography, (Lakhiari et al., Biochimica et Biophysica Acta, 1379:303-313 (1998)) development of a biohybrid artificial pancreas, (Vernon et al., Macromolecular Symposia, 109:155-167 (1996)) and cell growth for tissue regeneration (Stile et al., Biomacromolecules, 2:185-194 (2001); Stile et al., Abstracts of Papers of the American Chemical Society, 219:584-POLY (2000); Stile et al., Macromolecules, 32:7370-7379 (1999)). The evolution of most of these applications was based on the unique phase behavior of p(NIPAAm) in aqueous media. The linear polymer chains (in the case of a sIPN) or the second network (in the case of an IPN) were added to the p(NIPAAm)-based hydrogels to change the swelling characteristics and/or the mechanical properties of the matrices. To our knowledge, there are no publications to date in which the polymer chains or the second network were modified with biomolecules to impart biological functionality to the sIPN or IPN.
Previous work has led to the development of injectable p(NIPAAm-co-AAc) hydrogels that demonstrated a phase transition slightly below body temperature, during which the rigidity of the matrix significantly increased. During in vitro culture, these matrices supported bovine articular chondrocyte viability and promoted the formation of tissue with histoarchitecture similar to that of native articular cartilage. Furthermore, when the AAc groups in the p(NIPAAm-co-AAc) hydrogel were functionalized with peptides containing relevant sequences found in ECM macromolecules, the peptide-modified hydrogels supported rat calvarial osteoblast viability, spreading, and proliferation. However, the procedure used to functionalize the hydrogels with the peptide sequences adversely altered the volume change characteristics of the hydrogels, significantly limiting the clinical utility of these matrices.
In view of the advantages of sIPNs and the deficiencies of prior sIPNs, a sIPN that could be functionalized to interact with cells on a molecular level, or to serve as a drug delivery vehicle while maintaining predictable and useful swelling properties would represent a significant advance in the art. Surprisingly, the present invention provides such a sIPN.